Salmonella are facultative intracellular pathogens which cause significant diseases in humans and animals, these organisms cause several disease syndromes, including enteric (typhoid) fever, gastroenteritis, bacteremias and focal infections. Typhoid fever is a severe systemic illness which is mostly a problem in the developing world and in travelers. Non-typhoidal salmonella infections are increasing in the USA and are . largely associated with contaminated food. Salmonellaeinfections are most severe in infants, the elderly, and in immunosuppressed individuals. This grant proposes to study a set of virulence genes, termed Salmonella translocated effectors, that are translocated across the phagosome membrane into the eucaryotic cell cytoplasm by a type III secretion system encoded on Salmonella pathogenecity island II. This grant proposes to further define these proteins, and to study in molecular detail their role in bacterial virulence. This grant will test the hypothesis that these effectors modify the Salmonellae-containing vacuole to promote bacterial replication by altering host endocytic trafficking, inflammatory responses, and the vacuolar actin cytoskeleton.